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Biomedical subjects

W Smith

Publications and source records attributed to W Smith.

At least 37 records · Page 2Linked to original sources
PubMed2004

Fel d 4, a cat lipocalin allergen.

BACKGROUND: Cat allergy is unique among allergy to mammals in that the major allergen Fel d 1 is a uteroglobin-like protein and not a lipocalin. The biochemical spectrum of the cat allergens is thus uncertain, particularly with regard to the role that a cat lipocalin protein may play in sensitization to cats in allergic individuals. OBJECTIVE: To analyse cDNA encoding a lipocalin allergen and the corresponding recombinant allergen at both the molecular and immunological levels. METHODS: A submandibular salivary gland cDNA expression library was constructed and screened for clones producing IgE-binding polypeptides. cDNA encoding a lipocalin allergen and its corresponding recombinant allergen were analysed. RESULTS: An IgE binding molecule with high sequence identity to the boar salivary lipocalin and the horse lipocalin Equ c 1 allergen was isolated and designated, Fel d 4. Serum from 62.96% of cat-allergic subjects examined had measurable IgE antibody to Fel d 4 but typically at low levels. Despite this in 47% of sera the anti-Fel d 4 IgE titres were higher than the anti-Fel d 1 titres. IgE binding to the lipocalin allergen could be blocked by an allergen extract from cow and to a lesser degree by extracts from horse and dog. CONCLUSION: Fel d 4 is a lipocalin allergen produced by the cat, which binds IgE at relatively high frequency in cat-sensitive individuals. The allergen provides not only a means for investigating differences in the immune response to lipocalin allergens from that found for other mammalian species but also an important reagent for the diagnosis of cat allergy.

Allergens↗
PubMed2004

ASCIA guidelines for prevention of food anaphylactic reactions in schools, preschools and child-care centres.

These guidelines have been developed by the anaphylaxis working party of the Australasian Society of Clinical Immunology and Allergy to provide advice for minimizing the risk of food-induced anaphylaxis in schools, preschools and child-care centres. The guidelines outline four steps for the prevention of food anaphylactic reactions in children at risk and food policy measures specific to school age and preschool age children.

Age Factors↗
PubMed2003

Assessment of a cytology grading system for head and neck masses.

A grading system for Fine Needle Aspiration Biopsy Cytology (FNAC) has been in routine use in Peterborough since 1994 for reporting on fine needle aspiration biopsies of neck lumps. The records of all 276 patients who had neck lump fine needle aspiration biopsies performed between 1994 and 1999 were reviewed retrospectively. The 193 patients who had definitive histology available were included in the study of whom 154 (80.2%) were considered adequate for grading. A learning curve for adequacy of specimens obtained is demonstrated, with adequacy rate increasing with increasing experience or seniority of the sampler. The grading system produced an overall accuracy rate of 73.3% with a predictive value for malignancy of 88.6% and a predictive value for benign conditions of 67.3%. Individual grades were assessed for predictive value of benign or malignant disease. Grade 5 proved completely reliable, with a predictive value for malignancy of 100%. The shortcomings of the other grades and the difficulties in diagnosing lymphoma by FNAC are discussed.

Adolescent↗
PubMed2003

Preparation of site-specific cross-sections of heterogeneous catalysts prepared by focused ion beam milling.

Focused ion beam (FIB) milling offers a novel approach to preparation of site-specific cross-sections of heterogeneous catalysts for examination in the transmission electron microscope (TEM). Electron-transparent sections can be obtained without the need to embed or grind the original sample. Because the specimen can be imaged in the FIB with submicrometre resolution before, during and after milling it is possible to select precisely the region from which the section is removed and to control the thickness of the section to within tens of nanometres. The ability to produce sections in this way opens the possibility of studying a range of catalyst systems that have previously been impossible to examine with the TEM.

Journal Article↗
PubMed2002

Latent class analysis of symptoms associated with chronic fatigue syndrome and fibromyalgia.

BACKGROUND: Chronic fatigue syndrome and fibromyalgia continue to be perplexing conditions of unknown validity. Aetiological and symptomatic heterogeneity is likely and the distinctiveness of these disorders remains unclear. Our aims were to investigate empirically symptomatic heterogeneity in chronic fatigue syndrome and fibromyalgia. METHODS: Latent class analysis was applied to data from 646 patients who met accepted criteria for chronic fatigue syndrome and/or fibromyalgia who were systematically evaluated at a specialist fatigue clinic. Thirty-two symptoms commonly found in chronic fatigue syndrome and fibromyalgia were entered into the latent class analysis. RESULTS: We chose to interpret a four class solution. The classes appeared to differ in a graded fashion (rather than qualitatively) for symptom endorsements, pre-morbid characteristics, and co-morbidity with panic disorder and major depression. CONCLUSIONS: These results were unexpected given the usual assumption of the distinctiveness of chronic fatigue syndrome and fibromyalgia. These results support a conceptualization of chronic fatigue syndrome and fibromyalgia as being characterized by greater similarities than differences.

Adult↗
PubMed2002

Non-allergenic antigen in allergic sensitization: responses to the mite ferritin heavy chain antigen by allergic and non-allergic subjects.

BACKGROUND: The majority of house dust mite proteins are non-allergenic. There is, however, no information on the type of immune responses produced to these proteins and if the responses are affected by allergic sensitization. OBJECTIVE: To identify and produce a non-allergenic antigen of the house dust mite and compare antibody and T cell responses with the responses to allergens in sensitized and non-sensitized individuals. RESULTS: Ferritin heavy chain was cloned from a cDNA library as a candidate non-allergen of the house dust mite. It bound IgG but not IgE in the sera of allergic and non-allergic subjects and induced high T cell proliferative responses that correlated highly with the responses to the major allergen Der p 2. The cytokine response to the non-allergen was characterized by the release of high levels of both Th1 and Th2 cytokines from the PBMC of both allergic and non-allergic subjects. In contrast, the response to Der p 2 showed the expected high level of Th2 cytokine release from the PBMC of allergic subjects, while the Th2 cytokine production from PBMC of non-allergic subjects was low and even lower than that induced by ferritin heavy chain. The levels of IFN-gamma release were similar for all groups. Der p 2 induced significantly more IL-10 than ferritin in the non-allergic group. CONCLUSION: The T cell responses to a non-allergenic protein of the house dust mite were high and strongly correlated with the response to the major allergen. The non-allergenic protein induced high levels of Th1 and Th2 cytokine in both allergic and non-allergic subjects, while the allergen induced high levels of Th2 cytokine in allergic subjects and low levels in non-allergic subjects. The responses to the allergen were thus independently up- and down-regulated with no evidence of bystander regulation.

Adult↗
PubMed2002

Genetic variation of Der p 2 allergens: effects on T cell responses and immunoglobulin E binding.

BACKGROUND: Der p 2 is a highly polymorphic allergen that shows a distinct pattern of sequence divergence. The effect of the variations on T cell and antibody responses has not been compared. OBJECTIVES: To compare IgE antibody binding and T cell proliferation and cytokine release induced by variants of Der p 2. METHODS: Peripheral blood mononuclear cells (PBMC) from 19 allergic and 15 non-allergic people were stimulated with recombinant variants of Der p 2. IL-5, IL-10, IL-13 and IFN-gamma were measured by a time resolved fluorescence (TRF) assay. Serum IgE antibody was measured using a solid-phase TRF assay. RESULTS: Overall the most prevalent variant of Der p 2 (Der p 2. 0101) was the highest or approximately equal highest inducer of T cell proliferation and IL-5, IL-10, IL-13 and IFN-gamma release. The most divergent variant 0104 induced the next highest responses. The variants 0107 and 0108 showed interesting changes especially when the allergic status was considered. Responses to 0107 showed poor Th1/Th2 polarization and, except for IL-10 release, cytokine responses to 0108 were low for non-allergic subjects. The variant 0101 showed similar monoclonal antibody binding but moderately less IgE binding than the other variants. CONCLUSIONS: The most prevalent variant, Der p 2. 0101, was the most active for T cell stimulation and although its IgE binding was slightly less than other variants that was highly correlated. The variant Der p 2. 0104 which contains the known common polymorphic changes had a response which was similar to Der p 2. 0101 and thus these two variants were the most stimulatory representations of Der p 2. The T cell responses to the less common variants 0107 and 0108 however, showed consistent differences demonstrating that changes in the sequence could change the cytokine response.

Adult↗
PubMed2002

Raman and infrared studies of nucleosides at high pressures: II. Cytidine.

Raman and mid-infrared (MIR) spectra have been recorded for crystalline cytidine at pressures up to 10 GPa at room temperature. Broadening and positive wavenumber shifts are observed for most of the Raman and MIR peaks with increasing pressure. However, some of the MIR peaks associated with hydrogen-stretching modes display a negative wavenumber shift as a result of charge transfer effects. Evidence of a phase transition near 4 GPa is presented and attributed to a change in the conformation of the five membered sugar ring.

Cold Temperature↗
PubMed2001

Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial.

CONTEXT: Incidence of end-stage renal disease due to hypertension has increased in recent decades, but the optimal strategy for treatment of hypertension to prevent renal failure is unknown, especially among African Americans. OBJECTIVE: To compare the effects of an angiotensin-converting enzyme (ACE) inhibitor (ramipril), a dihydropyridine calcium channel blocker (amlodipine), and a beta-blocker (metoprolol) on hypertensive renal disease progression. DESIGN, SETTING, AND PARTICIPANTS: Interim analysis of a randomized, double-blind, 3 x 2 factorial trial conducted in 1094 African Americans aged 18 to 70 years with hypertensive renal disease (glomerular filtration rate [GFR] of 20-65 mL/min per 1.73 m(2)) enrolled between February 1995 and September 1998. This report compares the ramipril and amlodipine groups following discontinuation of the amlodipine intervention in September 2000. INTERVENTIONS: Participants were randomly assigned to receive amlodipine, 5 to 10 mg/d (n = 217), ramipril, 2.5 to 10 mg/d (n = 436), or metoprolol, 50 to 200 mg/d (n = 441), with other agents added to achieve 1 of 2 blood pressure goals. MAIN OUTCOME MEASURES: The primary outcome measure was the rate of change in GFR; the main secondary outcome was a composite index of the clinical end points of reduction in GFR of more than 50% or 25 mL/min per 1.73 m(2), end-stage renal disease, or death. RESULTS: Among participants with a urinary protein to creatinine ratio of >0.22 (corresponding approximately to proteinuria of more than 300 mg/d), the ramipril group had a 36% (2.02 [SE, 0.74] mL/min per 1.73 m(2)/y) slower mean decline in GFR over 3 years (P =.006) and a 48% reduced risk of the clinical end points vs the amlodipine group (95% confidence interval [CI], 20%-66%). In the entire cohort, there was no significant difference in mean GFR decline from baseline to 3 years between treatment groups (P =.38). However, compared with the amlodipine group, after adjustment for baseline covariates the ramipril group had a 38% reduced risk of clinical end points (95% CI, 13%-56%), a 36% slower mean decline in GFR after 3 months (P =.002), and less proteinuria (P<.001). CONCLUSION: Ramipril, compared with amlodipine, retards renal disease progression in patients with hypertensive renal disease and proteinuria and may offer benefit to patients without proteinuria.

Adrenergic beta-Antagonists↗
PubMed2001

Incidence of nursing home placement in a defined community.

OBJECTIVE: To assess cumulative incidence and non-cognitive factors predicting nursing home placement in a defined older population. DESIGN AND SETTING: Six-year follow-up of a population-based cohort living west of Sydney. PARTICIPANTS: 3654 non-institutionalised residents aged 49 years or older (82.4% of those eligible) participated in baseline examinations during 1992 to 1994. MAIN OUTCOME MEASURES: Permanent nursing home admission for long-term institutionalised aged care in New South Wales, confirmed by records of approvals by the regional Aged Care Assessment Team and subsidy payments by government. RESULTS: After excluding 384 participants who moved from the area or were lost to follow-up, 162 participants (5.0%) had been admitted to nursing homes on a permanent basis by October 1999. Of participants who died since baseline, 20% had been admitted to a nursing home before death. Of those alive, 1.6% were current nursing home residents. Six-year cumulative incidence rates for nursing home placement were 0.7%, 1.1%, 2.4%, 3.9%, 9.0%, 18.3% and 34.9% for people aged 55-59, 60-64, 65-69, 70-74, 75-79, 80-84 and 85 years or older, respectively. Non-cognitive factors at baseline predicting subsequent nursing home admission included each additional year of age (risk ratio [RR], 1.14), fair or poor compared with excellent self-rated health (RR, 2.9, 3.6), walking difficulty (RR, 3.6) and current smoking (RR, 1.9). People owning their homes had a decreased likelihood of nursing home placement (RR, 0.6). CONCLUSIONS: Incidence rates of institutional aged care doubled for each five-year interval from the age of 60 years. A range of non-cognitive factors predict nursing home placement.

Aged↗
PubMed2001

Visual impairment, age-related cataract, and mortality.

OBJECTIVE: To explore associations between visual impairment, cataract, and mortality in older persons after adjusting for other factors associated with mortality. METHODS: A population cohort of 3654 persons aged 49 years or older (82.4% of eligible residents in the Blue Mountains region, west of Sydney, Australia), were examined at the Blue Mountains Eye Study baseline period (1992-1994) and followed up 5 years later (1997-1999). Australian National Death Index data were used to confirm persons who had died since baseline. Associations between mortality and presence of visual impairment and cataract at baseline were assessed using the Cox proportional hazards regression model, controlling for age, sex, demographic and socioeconomic status, medical history, and health risk behaviors. RESULTS: By June 30, 1999, 604 participants (16.5%) had died. The age- and sex-standardized 7-year cumulative mortality rate was 26% among persons with any visual impairment and 16% in persons without visual impairment. After adjusting for factors found significantly associated with mortality, including age, male sex, low self-rated health, low socioeconomic status, systemic medical conditions, and negative health risk behaviors, the presence at baseline of any visual impairment was independently associated with increased mortality risk (risk ratio [RR], 1.7; 95% confidence interval, 1.2-2.3). The presence of age-related cataract, either nuclear (RR, 1.5), cortical (RR, 1.3), or posterior subcapsular cataract (RR, 1.5), was also significantly associated with increased mortality risk. These associations remained statistically significant when visual impairment and each type of cataract were included simultaneously in the multivariate Cox model. CONCLUSION: Visual impairment and age-related cataract may be independent risk factors for increased mortality in older persons.

Aged↗
PubMed2001

Risk factors for age-related macular degeneration: Pooled findings from three continents.

OBJECTIVE: To assess the prevalence and potential risk factors for late age-related macular degeneration (AMD) in three racially similar populations from North America, Europe, and AUSTRALIA: DESIGN: Combined analysis of population-based eye disease prevalence data. PARTICIPANTS: There were 14,752 participants with gradable photographs from the Beaver Dam Eye Study (n = 4756), Rotterdam Study (n = 6411), and Blue Mountains Eye Study (n = 3585). MAIN OUTCOME MEASURES: AMD diagnosis was made from masked grading of stereo macular photographs. Final classification of AMD cases was agreed by consensus between study investigators. RESULTS: AMD prevalence was strongly age related. Overall, AMD was present in 0.2% of the combined population aged 55 to 64 years, rising to 13% of the population older than 85 years. Prevalence of neovascular AMD (NV) increased from 0.17% among subjects aged 55 to 64 years to 5.8% for those older than 85 years. Prevalence of pure geographic atrophy (GA) increased from 0.04% to 4.2% for these age groups. There were no significant gender differences in the prevalence of NV or GA. Subjects in the Rotterdam population had a significantly lower age-adjusted and smoking-adjusted risk of NV than subjects in the Beaver Dam and Blue Mountains populations. Apart from age, tobacco smoking was the only risk factor consistently associated with any form of AMD in all sites separately and in pooled analyses over the three sites. CONCLUSIONS: These combined data from racially similar communities across three continents provide strong and consistent evidence that tobacco smoking is the principal known preventable exposure associated with any form of AMD.

Adult↗
PubMed2001

Folate fortification: potential impact on folate intake in an older population.

OBJECTIVE: To examine the potential impact of different models of folate fortification of Australian foods on the folate intakes of older Australians. DESIGN: Dietary data were collected using a food frequency questionnaire from people attending a population-based health study. SETTING: Two postcode areas west of Sydney, Australia. SUBJECTS: A total of 2895 people aged over 49 y, obtained from a door knock census (79% of 3654 subjects examined). MAIN OUTCOME MEASURES: The folate intake in this population was estimated using four different models: (1) pre-fortification folate values; (2) current voluntary folate fortification in Australia; (3) universal fortification of all foods permitted to add folate, at 25% recommended dietary intake (RDI) per reference serve; and (4) universal fortification of all foods permitted to add folate, at 50% RDI per reference serve. The increased bioavailability of synthetic folic acid (SFA) was included in the analysis. RESULTS: At current voluntary folate fortification, approximately 65% of this population consume 320 microg dietary folate equivalents (DFE) or more per day from diet and supplements, and 0.4% (n=10) consume greater than the recommended upper safety level of 1000 microg from SFA. More than 95% of this older population would be expected to consume more than 320 microg DFE from diet and supplements with universal fortification at 50% of the RDI, and 0.5% (n=14) may consume greater than 1000 microg/day of SFA. CONCLUSIONS: There is unlikely to be a large increase in the proportion of older persons who are likely to consume more than the upper safety level of intake with universal folate fortification. As most of those who currently or are predicted to consume over 1000 microg SFA take supplements containing folic acid, it is highly recommended that vitamin B12 be included in any vitamin supplements containing folate. SPONSORSHIP: This study was supported by the Australian National Health and Medical Research Council (NHMRC).

Aged↗
PubMed2001

PARP determines the mode of cell death in skin fibroblasts, but not keratinocytes, exposed to sulfur mustard.

Sulfur mustard is cytotoxic to dermal fibroblasts as well as epidermal keratinocytes. We demonstrated that poly(ADP-ribose) polymerase (PARP) modulates Fas-mediated apoptosis, and other groups and we have shown that PARP plays a role in the modulation of other types of apoptotic and necrotic cell death. We have now utilized primary dermal fibroblasts, immortalized fibroblasts, and keratinocytes derived from PARP(-/-) mice and their wildtype littermates (PARP(+/+)) to determine the contribution of PARP to sulfur mustard toxicity. Following sulfur mustard exposure, primary skin fibroblasts from PARP-deficient mice demonstrated increased internucleosomal DNA cleavage, caspase-3 processing and activity, and annexin V positivity, compared to those derived from PARP(+/+) animals. Conversely, propidium iodide staining, PARP cleavage patterns, and random DNA fragmentation revealed a dose-dependent increase in necrosis in PARP(+/+) but not PARP(-/-) cells. Using immortalized PARP(-/-) fibroblasts stably transfected with the human PARP cDNA or with empty vector alone, we show that PARP inhibits markers of apoptosis in these cells as well. Finally, primary keratinocytes were derived from newborn PARP(+/+) and PARP(-/-) mice and immortalized with the E6 and E7 genes of human papilloma virus. In contrast to fibroblasts, keratinocytes from both PARP(-/-) and PARP(+/+) mice express markers of apoptosis in response to sulfur mustard exposure. The effects of PARP on the mode of cell death in different skin cell types may determine the severity of vesication in vivo, and thus have implications for the design of PARP inhibitors to reduce sulfur mustard pathology.

Apoptosis↗